Haemolytic Uraemic Syndrome

Abstract

Atypical haemolytic uraemic syndrome (aHUS) is a disease characterized by complement overactivation in which inherited defects in complement genes and acquired autoantibodies against complement regulatory proteins have been described. Identification of the underlying defect can both predict disease outcome and guide treatment. The ability to remove inhibitory autoantibodies and hyper-active complement components in addition to its ability to replace defective complement regulators means that plasma exchange is currently first-line therapy. In those with factor H and factor I mutations who do progress to end-stage renal failure, renal transplantation usually fails due to recurrent HUS. In this situation, combined liver-kidney transplantation has been suggested to correct the underlying genetic defect. Newer agents, such as the complement inhibitor eculizumab, may herald a new era in the treatment of aHUS.

Indicators of Acute and Persistent Renal Damage in Adult Thrombotic Microangiopathy

“…Patients with atypical HUS may have a deficiency of complement factor H or auto-antibodies directed against this protein. Furthermore, mutations in the membrane cofactor protein gene (MCP/CD46), in the complement factor I gene, in the complement factor B gene or in the thrombomodulin gene may also be present [10], [11], [12]. In atypical HUS and selected Shiga-toxin-induced HUS cases the humanized monoclonal anti-C5 antibody eculizumab was reported to be beneficial [13], [14], [15].…”

Too Much of a Good Thing at the Site of Tissue Injury: The Instructive Example of the Complement System Predisposing to Thrombotic Microangiopathy

“…aHUS (or nonenteropathic HUS) is more severe, with an acute mortality up to 25% and often with recurrent episodes in which ϳ 50% of patients develop permanent kidney damage requiring long-term dialysis. [9][10][11][12][13][14][15][16][17][18] The penetrance is ϳ 50%, suggesting that an environmental factor is required to trigger the disease process. A serious infection in early childhood was found to be the most common precipitating event in several studies.…”

“…A serious infection in early childhood was found to be the most common precipitating event in several studies. [9][10][11][12][13][14][15][16][17][18][19] Whereas aHUS typically occurs in young children (mean age is less than 5 years), it may not manifest until later, particularly in association with pregnancy. The typical scenario for aHUS is that one parent, who has usually not developed aHUS, is a mutation carrier.…”

“…Alternatively, the protein is expressed but has reduced function. [9][10][11][12][13][14][15][16][17][18][19] The accumulated results in aHUS indicate that half normal levels of factor H or factor I predispose a child to a TMA. Interestingly, parents of aHUS patients, who are carriers, are usually healthy.…”

“…[28][29][30][31][32] Preeclampsia has been classified as a TMA based in part on the renal pathologic findings of endothelial cell swelling, expansion of the subendothelial zone, duplication of the glomerular basement membrane, mesangial cell interposition, and glomerular or microvascular thrombi. [13][14][15]18,19,27,29 Clinically, preeclampsia syndromes may be characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal involvement with refractory hypertension. Preeclampsia is a multifactorial syndrome that produces clinical symptoms with gradations of vasospasm, endothelial damage, and an inflammatory response.…”